中国河湟谷地进展期胃腺癌侵袭转移相关功能基因表达谱的筛选

The Screen of Gene Expression Profile Correlated to Invasion and Metastasis of Advanced Gastric Adenocarcinoma in Hehuang Valley of China

目的:筛选中国河湟谷地进展期胃癌侵袭转移相关功能基因差异性表达谱。方法:随机抽取世居于中国河湟谷地的新发胃癌病例共90例,提取手术切除的胃癌组织和癌旁组织中总RNA,反转录成cDNA并标记,并与肿瘤侵袭转移相关基因表达谱芯片杂交,经过扫描和数据分析,得出胃癌组织与癌旁组织中差异性表达基因谱。结果:经胃癌组织和癌旁组织基因差异性表达谱比较分析,胃癌组织中与肿瘤侵袭转移相关基因差异性表达量>2倍的共有36个。其中,7个细胞黏附基因(CD44、CDH1、CTNNA1、FXYD5、PNN、RPSA及VEGFA)表达上调,细胞外基质蛋白COL4A2、SERPINE1表达上调,MMP10、MMP13及TIMP4表达下调,细胞周期调控基因MYC、NME1表达上调,细胞生长与增殖调控基因CTBP1、DENR、MDM2、MET、SET及SRC上调,而CCL7、HGF、KISS1R、RORB、SSTR2、TRPM1及TSHR下调,转录调控基因CHD4、EWSR1、FN1及SMAD2表达上调,此外,CTSK、CTSL1及METAP2表达上调,KISS1及THBS33下调。结论:胃腺癌侵袭转移相关功能基因差异性表达谱的筛选,为进一步研究中国河湟谷地进展期胃癌的分子机制确定了方向。

Objective. The purpose of this study is to screen the gene expression profile correlated to inva- sion and metastasis of advanced gastric adenocarcinoma in Hehuang Valley of China.Methods：90 cases with advanced gastric adenocarcinoma from Hehuang Valley were randomly collected. The total RNA of gastric adenocarcinoma tissue corresponding para--cancer tissue was isolated and labeled by reverse transcription reaction for cDNA. The labeled cDNA was hybridized with cDNA microarray. After scanning and analyzing the data, the different gene expression profile of advanced gastric adenocarcinoma and para--cancer tissue was investigated.Results：Being compared of the different gene expression profile in advanced gastric adeno- carcinoma and para- gastric adenocarcinoma, there were total of 36 genes with more than two fold changed expression in advanced gastric adenocarcinoma, which included 24 upregulated of genes as fol- lowed ： cell adhesion genes （CD44, CDH1, CTNNA1, FXYD5, PNN, RPSA and VEGFA）, extracellular matrix proteins （COL4A2 and SERPINE1）, cell cycle genes （MYC and NME1）, cell growth and prolifer- ation genes （CTBP1, DENR, MDM2, MET, SET and SRC）, transcription factors and regulators （CHD4, EWSR1, FN1 and SMAD2） and other genes related to metastasis （CTSK, CTSL1 and METAP2）. In addition, 12 downregulated of genes also showed in advanced gastric adenocarcinoma as fol- lowed= extracellular matrix proteins （MMP10, MMP13 and TIMP4）, cell growth and proliferation genes （CCL7, HGF, KISSIR, RORB, SSTR2, TRPM1 and TSHR） and other genes related to metastasis （KISS1 and THBS33）.Conclusions： It can help us to further study the molecular mechanism of gastric ade- nocarcinoma by the gene expression profile correlated to invasion and metastasis of advanced gastric adeno- carcinoma in Hehuang Valley of China.